Comparison of Combination Chemotherapy Regimens in Treating Older Women Who Have Undergone Surgery for Breast Cancer

• Relapse-free Survival Rates at 2.4 Years [ Time Frame: randomization until date of first event, or date last known to be event free if no event was reported (up to 5 years) ] [ Designated as safety issue: No ]
  Percentage of participants who were alive and relapse-free at time of analysis were counted as "Alive without relapse" at 2.4 years. Participants who had a first local recurrence, first distant metastasis or death from any cause were counted as "relapse, first occurrence". These rates were estimated using the Kaplan Meier method
  
  

• Overall Survival Rate at 2.4 Years [ Time Frame: Time from registration to death (up to 15 years) ] [ Designated as safety issue: No ]
  Percentage of patients who were alive at 2.4 years. This rate was estimated using the Kaplan Meier method.
  
  
• Number of Participants With Grade 3, 4 or 5 Adverse Event at Least Possibly Related to Treatment. [ Time Frame: Reported during protocol treatment after each cycle ] [ Designated as safety issue: Yes ]

  The National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Version 2.0 was used to evaluate toxicity.

  Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life Threatening; Grade 5: Death.

  
  

OBJECTIVES:

• Compare the effectiveness of adjuvant chemotherapy comprising standard cyclophosphamide, methotrexate, and fluorouracil (CMF) or doxorubicin and cyclophosphamide (AC) vs oral capecitabine, in terms of disease-free and overall survival, in elderly women with operable adenocarcinoma of the breast.
• Compare the quality of life and physical functioning of patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Evaluate the adherence of older patients to an oral chemotherapy regimen.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (65 to 69 vs 70 to 80 vs over 80), performance status (0-1 vs 2), and HER2 status (positive vs negative vs unknown). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients with insufficient left ventricular ejection fraction (LVEF) are assigned to group A. Patients with normal LVEF are assigned to group A or B based on physician/patient choice.

  • Group A (CMF): Patients receive oral cyclophosphamide (CTX) daily on days 1-14 and methotrexate IV and fluorouracil IV on days 1 and 8. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
  • Group B (AC): Patients receive doxorubicin IV and CTX IV on day 1. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive oral capecitabine twice daily on days 1-14. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

Beginning within 12 weeks after treatment in arm I or II, patients with estrogen or progesterone receptor-positive disease receive oral tamoxifen or an aromatase inhibitor daily for 5 years.

Beginning 4-6 weeks after treatment in arm I or II, eligible patients who previously underwent breast conservation surgery undergo radiotherapy.

Quality of life is assessed at baseline; at 6 weeks (group B), 9 weeks (arm II), or 12 weeks (group A); and then at 1, 12, 18, and 24 months after study.

Drug adherence is assessed at 9 weeks during study (arm II).

Patients are followed at 1 month, every 6 months for 2 years, and then annually for 15 years.

PROJECTED ACCRUAL: A total of 600-1,800 patients (300-900 per treatment arm) will be accrued for this study within 2-6 years.